Do Genetic Factors Modify the Relationship Between Obesity and Hypertriglyceridemia? Findings From the GLACIER and the MDC Studies
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Do Genetic Factors Modify the Relationship Between Obesity and Hypertriglyceridemia? Findings From the GLACIER and the MDC Studies. / Ali, Ashfaq; Varga, Tibor V; Stojkovic, Ivana A; Schulz, Christina-Alexandra; Hallmans, Göran; Barroso, Inês; Poveda, Alaitz; Renström, Frida; Orho-Melander, Marju; Franks, Paul W.
In: Circulation. Cardiovascular genetics, Vol. 9, No. 2, 04.2016, p. 162-171.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Do Genetic Factors Modify the Relationship Between Obesity and Hypertriglyceridemia?
T2 - Findings From the GLACIER and the MDC Studies
AU - Ali, Ashfaq
AU - Varga, Tibor V
AU - Stojkovic, Ivana A
AU - Schulz, Christina-Alexandra
AU - Hallmans, Göran
AU - Barroso, Inês
AU - Poveda, Alaitz
AU - Renström, Frida
AU - Orho-Melander, Marju
AU - Franks, Paul W
N1 - © 2016 American Heart Association, Inc.
PY - 2016/4
Y1 - 2016/4
N2 - BACKGROUND: Obesity is a major risk factor for dyslipidemia, but this relationship is highly variable. Recently published data from 2 Danish cohorts suggest that genetic factors may underlie some of this variability.METHODS AND RESULTS: We tested whether established triglyceride-associated loci modify the relationship of body mass index (BMI) and triglyceride concentrations in 2 Swedish cohorts (the Gene-Lifestyle Interactions and Complex Traits Involved in Elevated Disease Risk [GLACIER Study; N=4312] and the Malmö Diet and Cancer Study [N=5352]). The genetic loci were amalgamated into a weighted genetic risk score (WGRSTG) by summing the triglyceride-elevating alleles (weighted by their established marginal effects) for all loci. Both BMI and the WGRSTG were strongly associated with triglyceride concentrations in GLACIER, with each additional BMI unit (kg/m(2)) associated with 2.8% (P=8.4×10(-84)) higher triglyceride concentration and each additional WGRSTG unit with 2% (P=7.6×10(-48)) higher triglyceride concentration. Each unit of the WGRSTG was associated with 1.5% higher triglyceride concentrations in normal weight and 2.4% higher concentrations in overweight/obese participants (Pinteraction=0.056). Meta-analyses of results from the Swedish cohorts yielded a statistically significant WGRSTG×BMI interaction effect (Pinteraction=6.0×10(-4)), which was strengthened by including data from the Danish cohorts (Pinteraction=6.5×10(-7)). In the meta-analysis of the Swedish cohorts, nominal evidence of a 3-way interaction (WGRSTG×BMI×sex) was observed (Pinteraction=0.03), where the WGRSTG×BMI interaction was only statistically significant in females. Using protein-protein interaction network analyses, we identified molecular interactions and pathways elucidating the metabolic relationships between BMI and triglyceride-associated loci.CONCLUSIONS: Our findings provide evidence that body fatness accentuates the effects of genetic susceptibility variants in hypertriglyceridemia, effects that are most evident in females.
AB - BACKGROUND: Obesity is a major risk factor for dyslipidemia, but this relationship is highly variable. Recently published data from 2 Danish cohorts suggest that genetic factors may underlie some of this variability.METHODS AND RESULTS: We tested whether established triglyceride-associated loci modify the relationship of body mass index (BMI) and triglyceride concentrations in 2 Swedish cohorts (the Gene-Lifestyle Interactions and Complex Traits Involved in Elevated Disease Risk [GLACIER Study; N=4312] and the Malmö Diet and Cancer Study [N=5352]). The genetic loci were amalgamated into a weighted genetic risk score (WGRSTG) by summing the triglyceride-elevating alleles (weighted by their established marginal effects) for all loci. Both BMI and the WGRSTG were strongly associated with triglyceride concentrations in GLACIER, with each additional BMI unit (kg/m(2)) associated with 2.8% (P=8.4×10(-84)) higher triglyceride concentration and each additional WGRSTG unit with 2% (P=7.6×10(-48)) higher triglyceride concentration. Each unit of the WGRSTG was associated with 1.5% higher triglyceride concentrations in normal weight and 2.4% higher concentrations in overweight/obese participants (Pinteraction=0.056). Meta-analyses of results from the Swedish cohorts yielded a statistically significant WGRSTG×BMI interaction effect (Pinteraction=6.0×10(-4)), which was strengthened by including data from the Danish cohorts (Pinteraction=6.5×10(-7)). In the meta-analysis of the Swedish cohorts, nominal evidence of a 3-way interaction (WGRSTG×BMI×sex) was observed (Pinteraction=0.03), where the WGRSTG×BMI interaction was only statistically significant in females. Using protein-protein interaction network analyses, we identified molecular interactions and pathways elucidating the metabolic relationships between BMI and triglyceride-associated loci.CONCLUSIONS: Our findings provide evidence that body fatness accentuates the effects of genetic susceptibility variants in hypertriglyceridemia, effects that are most evident in females.
KW - Body Mass Index
KW - Female
KW - Gene Regulatory Networks
KW - Genetic Predisposition to Disease
KW - Genome-Wide Association Study
KW - Humans
KW - Hypertriglyceridemia/blood
KW - Life Style
KW - Male
KW - Middle Aged
KW - Obesity/blood
KW - Polymorphism, Single Nucleotide/genetics
KW - Risk Factors
KW - Sex Characteristics
KW - Triglycerides/blood
U2 - 10.1161/CIRCGENETICS.115.001218
DO - 10.1161/CIRCGENETICS.115.001218
M3 - Journal article
C2 - 26865658
VL - 9
SP - 162
EP - 171
JO - Circulation: Cardiovascular Genetics
JF - Circulation: Cardiovascular Genetics
SN - 1942-325X
IS - 2
ER -
ID: 242837863